Many details of the circuitry and physiologic processes underlying the temperature regulation responses are now known, and they indicate that the preoptic area and dorsal medial hypothalamic nucleus are key components in the regulation of body temperature. The preoptic area in particular appears to be the target of the various sources of sensory information. Cutaneous temperature information is conveyed by thermosensitive primary afferents that synapse in the dorsal horn of the spinal cord onto neurons that project up to and excite the parabrachial nucleus in the caudal midbrain. Information from visceral afferents is relayed by the solitary nucleus to the parabrachial nucleus as well. The parabrachial neurons in turn excite neurons within a specific part of the preoptic area, the median nucleus (of the preoptic area). Many median nucleus neurons are also sensitive to local changes in blood temperature and contain prostaglandin E2 (PGE2) receptor 3 (EP3), which mediates fever responses (see the following “In the Clinic” box).
Thus the median preoptic nucleus is a key component of the thermoregulatory control system in which information from the various types of thermoreceptors is integrated. Output from this nucleus is directed to the neighboring medial preoptic area, which projects to regions of the rostral medulla, both directly and via the dorsal medial hypothalamic nucleus. The rostral medulla has spinally projecting neurons that project to the lateral horn of the spinal cord, where the preganglionic sympathetic neurons are located, and the activity of these neurons regulates BAT thermogenesis and modulates cutaneous vasomotor tone. The rostral medulla also projects to the ventral horn of the spinal cord, which contains the somatic motor neurons that contract skeletal muscle and thus mediate the shivering response.
Fever,whichaccompaniessomeinfections,canbethoughtofasanelevationofthesetpointforbodytemperature.Thiselevationcanbecausedbythereleaseofpyrogens bymicroorganismsorbycellsmediatingtheinflammatoryresponse.Thepyrogen’seffecttoraisethesetpointismediatedprimarilybytheactionofprostaglandinPGE2’sbindingtoEP3receptorsonneuronsinthepreopticarea.PGE2isreleasedbyperipheraltissuesandbybloodvesselssupplyingthepreopticarea.ThebindingofPGE2toEP3receptorscausesareductionintheactivityofpreopticneurons.ThisreductioninneuronalactivityleadstoincreasedheatproductionthroughshiveringandBATthermogenesisandtoheatconservationbycutaneousvasoconstriction,thecombinedeffectofwhichistoraisebodytemperature.EvidenceofthismechanismoffeverproductionincludesstudiesinwhichinjectionofPGE2intothepreopticareainducedfeverandothersinwhichselectivedeletionoftheEP3receptorfrompreopticneuronsabolishedtheabilityofPGE2injectionstoinducefever.
Regulation of Feeding and Body Weight
Energy homeostasis is crucial for the survival of the animal. The challenge is that most cells need a continuous supply of nutrients to function, but most animals do not constantly eat; instead, they have periodic meals. Thus to achieve energy homeostasis, feeding behavior is controlled by many factors, which operate both on a short-term basis to control ingestion and on a long-term basis to control body weight in order to ensure sufficient energy stores. Both hedonic and homeostatic factors are involved; however, in this chapter, the focus is on the latter because of the central role that the hypothalamus plays in energy homeostasis.